An aim of modern medicine is to provide personalized or individualized treatment regimens. Those are treatment regimens which take into account a patient's individual needs or risks. Personalized or individual treatment regimens shall be even taken into account for measures where it is required to decide on potential treatment regimens.
Heart failure is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. Even with the best therapy, heart failure is associated with an annual mortality of about 10%. Therefore, heart failure patients require close medical management in order to ameliorate their condition or to prevent the progression of their condition and to reduce morbidity and mortality. The medical management of heart failure patients includes the administration of drugs as well as diagnostic interventions such as coronary angiography.
Improvements during the last decades in heart failure therapy contributed to a larger life expectancy of patients suffering from heart failure. E.g., the survival of patients with heart failure can be increased by administration of angiotensin-converting enzyme (ACE) blockers, beta blockers, angiotensin receptor blockers and spironolactone. However, the administration of certain pharmaceuticals for the treatment of heart failure and for the treatment of comorbidities of heart failure may impair renal function. Therefore, heart failure patients receiving treatment should be regularly monitored for their renal function and treatment should be adjusted accordingly.
ACE inhibitors are frequently used for the treatment of heart failure since they have been clinically shown to be superior to other classes of drugs regarding the reduction of mortality.
In general, ACE inhibitors are renoprotective. However, acute rises in serum creatinine levels are observed in up to 30 percent of patient with first two months of therapy. It is known that renal impairment is a significant adverse effect of ACE inhibitors since some patients taking ACE inhibitor suffer from acute renal failure (Abuelo. N Engl J Med 2007; 357:797-805; Lameire et al., Lancet 2005; 365: 417-30). These adverse side effects are linked to the effect of ACE inhibitors on angiotensin II-mediated functions such as renal blood flow which is affected by angiotensin II because angiotensin II vasoconstricts the efferent arterioles of the glomeruli of the kidney, and thereby increases glomerular filtration rate (GFR), a marker for renal function.
In addition to ACE inhibitors there are further drugs against heart failure which may affect renal function, particularly, NSAIDs, diuretics and antihypertensive drugs. These drugs may also result in an acute increase of serum creatinine concentration due to renal ischemia. Therefore, Abuele (loc. cit.) recommends to closely monitor patients taking these drugs, or even to stop the therapy. Stopping the therapy may be beneficial for renal function, but may worsen the condition of the patient with respect to the heart.
The effect on renal function may even be increased when concomitantly taking other pharmaceuticals such as ACE inhibitors and non-steroidal anti-inflammatory drugs.
Renal function can be assessed by determining the glomerular filtration rate (GFR). However, the determination of the GFR is very difficult, time- and cost-intensive. Therefore, renal function is typically assessed by determining the serum creatinine concentration or by assessing changes in the serum creatinine concentration. The use of creatinine as a marker for renal function, however, has been recently put into jeopardy as the serum creatinine concentration is not necessarily an accurate reflection of true renal function because the concentration also depends on other factors like age and gender. Moreover, an increase of serum creatinine levels is frequently observed only after a marked damage to functioning nephrons. Therefore, this test is not suitable for detecting early stages of renal impairment.
Thus, adverse side effects can accompany the benefits in patients with heart failure taking medication against heart failure. Therefore, it is necessary to balance the benefits of a heart failure related therapy against adverse side effects on renal function that may be caused by the therapy. Particularly, there is a need for assessing both renal function and heart function in patients with heart failure in order to adjust the dosage regimen of certain pharmaceuticals used for the treatment of heart failure.
However, although highly desirable, means and methods allowing for a reliable and efficient identification of subjects being susceptible to a cardiac therapy are not yet available.
The technical problem underlying the present invention can be seen as the provision of means and methods for complying with the aforementioned needs. The technical problem is solved by the embodiments characterized in the claims and herein below.